Cytokine loops involving interferon-γ and IP-10, a cytokine chemotactic for CD4+ lymphocytes: An explanation for the epidermotropism of cutaneous T- cell lymphoma?

A. H. Sarris, T. Esgleyes-Ribot, M. Crow, H. E. Broxmeyer, N. Karasavvas, W. Pugh, D. Grossman, A. Deisseroth, M. Duvic

Research output: Contribution to journalArticle

73 Scopus citations

Abstract

Human interferon-γ (IFN-γ)-inducible protein 10 (IP-10), a C-X-C chemokine, is secreted by IFN-γ-stimulated keratinocytes and is chemotactic for CD4+ lymphocytes. We therefore investigated its role in the epidermotropism of cutaneous T-cell lymphoma (CTCL) that is known to express IFN-γ mRNA in the epidermis and is characterized by an indolent course with multiple relapses that remain confined to the skin for many years. By injecting purified recombinant (r) IP-10 we generated a polyclonal rabbit antiserum that specifically recognized and neutralized rIP-10. With immunoperoxidase staining, IP-10 expression was limited to the basal epidermal keratinocytes of normal skin. In biopsies of CTCL lesions the expression of IP-10 was markedly increased and it extended to the suprabasal keratinocytes in 17 of 18 patients, but it was detectable only faintly in the dermal or epidermal lymphoid infiltrates in 2 of these 18 patients. In 1 patient who had matching biopsies performed before and after treatment, IP- 10 was overexpressed before treatment, but was normally expressed in the posttreatment biopsy that showed resolution of the CTCL. Increased IP-10 expression was not detected in any of 4 patients with B-cell lymphoma involving the dermis. On the basis of these findings and a review of the literature, we propose that secretion of IFN-γ by the lymphoid infiltrate in CTCL induces the epidermal keratinocytes to secrete IP-10 that, in turn, is chemotactic for CTCL, accounting for its epidermotropism. This model may be used as a basis for future investigations of the pathogenesis of CTCL.

Original languageEnglish (US)
Pages (from-to)651-658
Number of pages8
JournalBlood
Volume86
Issue number2
DOIs
StatePublished - 1995

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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